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PubMed1996

Ovarian reserve test with the gonadotrophin-releasing hormone agonist buserelin: correlation with in-vitro fertilization outcome.

A gonadotrophin-releasing hormone agonist stimulation test determination of follicle stimulating hormone (FSH) concentrations before and 2 h after buserelin injection was carried out in 78 in-vitro fertilization cycles, and compared with basal FSH concentrations to predict ovarian response. Ovarian response was quantified by the ratio of peak oestradiol concentration divided by the total dose of human menopausal gonadotrophin (HMG) administered, the most reproducible parameter in 11 patients who underwent two treatment cycles. Stimulation outcome was highly related to the buserelin test, the best prognostic indicator being the sum of FSH concentrations. However, basal FSH concentration achieved similar correlations, even in those patients aged > 35 years. Sensitivity, specificity, positive and negative predictive values of basal FSH concentration and sum of FSH concentrations were similar. Low basal concentration and sum of FSH concentrations were both associated with a better ovarian response. Construction of receiver operator characteristic curves demonstrated that basal FSH concentration was more informative than the sum of FSH concentrations. Finally, the sum of FSH concentrations did not increase the prediction of ovarian response variability. We conclude that the buserelin test is strongly predictive of stimulation outcome, but is no more informative than the usual screening. We suggest that the performance of other stimulation tests should be clearly compared with that of basal FSH concentration.

Adult↗
PubMed1990

Cytogenetic analysis of unfertilized oocytes retrieved after treatment with the LHRH analogue, buserelin.

Chromosome analysis is reported on 155 oocytes from an in-vitro fertilization (IVF) programme in which the LHRH analogue, buserelin, was used in the superovulation regime. Seventy-one oocytes had the normal number of metaphase II chromosomes. Hyperhaploidy was apparent in four cases only; doubling this figure to include the reciprocally formed hypohaploid oocytes gave an aneuploidy rate due to non-disjunction of 10%. This is close to the figure for naturally occurring aneuploidy which may be calculated from data on recognized conceptions at a comparable maternal age. Taken together with the suggestion of a maternal age effect in our series these data suggest that follicular stimulation regimes which precede IVF do not necessarily add to the naturally high aneuploidy rate of the human species. Thirteen oocytes had failed to form the first polar body and the presence of diploid mitotic or sperm chromosomes provided evidence of fertilization and arrested development in 15. These figures for chromosomal anomalies following buserelin treatment are not significantly different from those obtained from comparable surveys following clomiphene citrate stimulation, providing no evidence that the improved pregnancy rate with buserelin is due to chromosomal factors.

Adult↗
PubMed1993

Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin.

To assess the risk of miscarriage after in-vitro fertilization (IVF) with respect to age, cause of infertility, ovarian morphology and treatment regimen, a retrospective analysis was performed of the first 1060 pregnancies conceived between June 1984 and July 1990 as a result of 7623 IVF cycles. Superovulation induction was achieved with human menopausal gonadotrophin (HMG) and/or purified follicle stimulating hormone (FSH) together with either clomiphene citrate or the gonadotrophin hormone-releasing hormone (GnRH) agonist buserelin, the latter either as a short 'flare' regimen or as a 'long' regimen to induce pituitary desensitization. There were 282 spontaneous abortions (26.6%) and 54 ectopic pregnancies (5.1%). The mean age of women with ongoing pregnancies was 32.2 (SD 3.9) years compared with 33.2 (SD 4.1) years in those who miscarried, which were significantly different (P = 0.008). There was no relation between the miscarriage rate and the indication for IVF. The miscarriage rate was 23.6% in women with normal ovaries compared with 35.8% in those with polycystic ovaries [P = 0.0038, 95% confidence interval (CI) 4.68-23.10%]. There was no difference in the miscarriage rate between treatment with HMG or FSH. Women whose ovaries were normal on ultrasound were just as likely to miscarry if they were treated with clomiphene or with the long buserelin protocol. Those with polycystic ovaries, however, had a significant reduction in the rate of miscarriage when treated with the long buserelin protocol, 20.3% (15/74), compared with clomiphene citrate, 47.2% (51/108) (P = 0.0003, 95% CI 13.82-40.09%).

Abortion, Spontaneous↗
PubMed1994

Progesterone-induced urticaria: response to buserelin.

We report a 41-year-old Caucasian woman with polycystic liver and kidney disease, and a 9-year history of severe cyclical urticaria related to her menses. The urticaria was not adequately controlled by antihistamines or Prempak-C (conjugated oestrogens and norgestrel). Intradermal testing with progesterone was strongly positive at 30 min and 18 h. Buserelin, administered intranasally at doses of up to 800 micrograms daily, controlled the urticaria within 4 weeks, and she was completely symptom-free thereafter. She had therapy-induced amenorrhoea and occasional hot flushes. Unfortunately, her liver cysts progressively enlarged, and a right hepatectomy was performed in June 1992, but she died after complications 3 weeks later. Prior to this she had been free of urticaria for 6 months after starting buserelin. Buserelin, a gonadotrophin-releasing hormone analogue, may be useful in the management of progesterone-induced urticaria, in patients in whom conjugated oestrogens are contraindicated or unhelpful.

Adult↗
PubMed1988

Reversible trabecular bone density loss following induced hypo-oestrogenism with the GnRH analogue buserelin in premenopausal women.

Thirteen premenopausal women who each received 400 micrograms three times daily of intranasal buserelin for 6 months as treatment for endometriosis participated in this study. Cortical bone mineral content (BMC) in the mid-shaft of the right femur measured by dual photon densitometry, and trabecular bone density (TBD) in the lumbar vertebrae (L2-4) measured by quantitative computed tomography, were evaluated prior to, at the end of 6 months' buserelin treatment and after 6 months off treatment. Significant hypo-oestrogenism (P less than 0.001) was sustained during the period on treatment. The significant reduction in the mean lumbar vertebral TBD of 5.9% (P less than 0.02) observed at the end of treatment with buserelin was regained within 6 months following resumption of ovarian activity. There was a marginally significant (P = 0.07) reduction of only 0.9% in the mean femoral cortical BMC at the end of treatment. Six months after the end of treatment cortical BMC values were not significantly different from the pretreatment values. There was no significant correlation between the degree of hypo-oestrogenism and the corresponding change in vertebral TBD, (r = 0.20; P less than 0.10).

Adult↗
PubMed1988

Non-specific histamine release activity of busereline, LH-releasing hormone.

Busereline acetate is an LH-RH agonist that was found to induce local reactions at the injection site or generalized minor skin reactions in some patients. Since these reactions may represent the first reaction of systemic anaphylaxis, we tested the non-specific histamine releasing activity of this drug by intradermal skin tests. It was found that all subjects tested had a positive wheal and flare reaction, the flare being significantly decreased by terfenadine. Benzyl alcohol, the preservative used in commercial preparation of busereline acetate, did not elicit a positive wheal and flare reaction in two patients who had experienced a clinically noticeable reaction. It is concluded that busereline is likely to be a non-specific histamine releasing compound.

Adult↗
PubMedDate not supplied

Effect of constant infusion of gonadotropin releasing hormone (GnRH) agonist buserelin and antagonist CDB 2085 A using osmotic minipumps on testicular function in adult male bonnet monkey (Macaca radiata).

The effect of chronic infusion of gonadotropic hormone agonist Buserelin or antagonist CDB 2085 A for 15 weeks via alzet minipumps in adult male bonnet monkeys was studied. Infusion of Buserelin resulted in a decrease in the difference between serum testosterone values at 22.00 hours and 10.00 hours, decrease in responsiveness to injected Buserelin as judged by change in serum testosterone values from pre-injection values and decrease in sperm counts. Infusion of antagonist resulted in a decrease in the difference between serum testosterone values at 22.00 hours and 10.00 hours.

Amino Acid Sequence↗
PubMed1990

Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial.

A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

Administration, Inhalation↗
PubMed1990

Controlled ovarian hyperstimulation for in vitro fertilization using buserelin and gonadotropin in patients with previous failed cycles.

Fifteen patients who had had previous unsuccessful in vitro fertilization and embryo transfer (IVF) cycles were treated with intranasal buserelin, a gonadotropin releasing hormone agonist (GnRH-a), commencing in the mid-luteal phase prior to ovarian stimulation in the next cycle. The use of buserelin was associated with the suppression of spontaneous luteinizing hormone (LH) surges (nil versus 6), an increase in gonadotropin requirements (27.3 versus 13.7 ampoules), higher serum estradiol peak levels (8, 154 versus 4,446 pmol/l), more oocytes retrieved (87 versus 20) as well as more embryos being transferred (28 versus 7). In buserelin-treated cycles, 2 pregnancies resulted but no oocyte was recovered in 2 of the 3 poor responders.

Adult↗
PubMed1993

Luteinizing hormone (LH) surge in patients using buserelin spray during ovarian stimulation for assisted reproduction.

The incidence of luteinizing hormone surge was studied in patients who were downregulated with a short protocol of gonadotrophin releasing hormone agonist before ovarian stimulation for assisted reproduction. Buserelin nasal spray 100 micrograms was given 5 times daily from day 2 of the cycle, followed by ovarian stimulation with human menopausal gonadotrophin and follicle stimulating hormone from day 3 onwards. Of the 159 cycles studied, luteinizing hormone surge was detected in 9 cycles (5.7%). The occurrence of LH surge was usually (67%) but not always associated with a fall in serum oestradiol level before administration of human chorionic gonadotrophin. None of the patients developed luteinizing hormone surge after day 10. Even in patients without luteinizing hormone surge the serum luteinizing hormone levels on the day of administration of hCG were significantly higher than those on day 2 before administration of buserelin. It is concluded that a short protocol with intranasal buserelin 500 micrograms per day is inadequate to suppress endogenous luteinizing hormone surge.

Administration, Intranasal↗
PubMed1999

Rates of endometriosis recurrence and pregnancy 1 year after treatment with intranasal buserelin acetate (Suprecur) (a prospective study).

OBJECTIVES: This multicenter prospective study of buserelin acetate (Suprecur) therapy for endometriosis was performed in order to examine pregnancy rates and the recurrence of endometriosis 1 year after the end of intranasal administration. METHODS: This study was conducted at 349 institutions, including university hospitals and major hospitals in Japan, and 1,284 patients were recruited as participants. Recurrence of symptoms was followed for 1 year after the end of administration of buserelin acetate in patients whose condition as a whole was evaluated as "improved" or better at the end of administration. Furthermore, the pregnancy rate was similarly followed in patients who complained of sterility at the commencement of the administration. Recurrence was defined as either a case in which all of the main symptoms observed before administration returned to the pretreatment state, or a case in which at least one symptom deteriorated compared to the pretreatment state. Kaplan-Meier's method was used for statistical analysis. RESULTS: Among 459 patients who could be evaluated for recurrence of symptoms, the cumulative recurrence rate was 17.8% 1 year after the end of administration. Among 156 patients who could be evaluated for pregnancy, the pregnancy rate was 23.3% 1 year after the end of administration. CONCLUSION: Intranasal buserelin acetate therapy exhibited not only transient clinical effects during administration or immediately after the end of administration, but also exhibited specific continuing effects after the end of administration.

Administration, Intranasal↗
PubMed1989

Long-term follow-up of patients with uterine fibroids after treatment with the LHRH agonist buserelin.

Ten patients with uterine fibroids palpable abdominally were treated with the luteinizing hormone-releasing hormone (LHRH) agonist buserelin, administered intransally, 300 micrograms three times daily, for 6 months, and were then followed for a further 12 months. Oestrogen levels were markedly reduced in all patients during treatment. At the end of treatment the mean volume reductions were 44.4% (SEM 3.5) for total uterine volume and 57.3% (SEM 7.4) for volume of discrete fibroids as assessed ultrasonically. There was also marked improvement in associated symptoms. After buserelin therapy was stopped, the total uterine and discrete fibroid volumes returned to, or slightly exceeded, pretreatment volumes within 6 months in five patients, and by 12 months in two patients. Three other patients who underwent surgery for their fibroids during the first 4 months after treatment showed regrowth of fibroids to pretreatment size. Four comparable asymptomatic untreated patients showed no significant change in the total uterine or fibroid volume during six monthly ultrasonic assessments. Buserelin therapy may facilitate rather than replace surgery in the management of uterine fibroids.

Adult↗
PubMed1991

The use of the GnRH analogue buserelin for IVF--does it improve fertility?

OBJECTIVE: To determine the effect of a short course of the GnRH analogue buserelin and human menopausal gonadotrophin (hMG), for ovarian stimulation in our IVF programme, on reproductive endocrinology and pregnancy rates compared with conventional clomiphene citrate and hMG treatment. DESIGN: Prospective randomized allocation to one of two ovulation stimulation regimens. SETTING: Fertility clinic. SUBJECTS: 373 infertile couples with various factors associated with their subfertility. All the women were less than 46 years of age and had normal menstrual cycles. INTERVENTION: The first group (n = 151) was given clomiphene citrate (CC) from days 2-6 of the menstrual cycle and hMG from day 5 onwards (CC/hMG). The second group (n = 222) was given buserelin from days 1-3 and hMG from day 2 (buserelin/hMG). MAIN OUTCOME MEASURES: Concentration of plasma luteinizing hormone (LH), oestradiol (E2) and progesterone, number of ovulatory follicles induced and the occurrence of pregnancy. RESULTS: Plasma LH, E2 and progesterone concentrations were reduced in the late follicular phase after buserelin/hMG compared with CC/hMG. Buserelin/hMG promoted the development of more follicles than CC/hMG. The overall pregnancy rate after buserelin/hMG was not significantly different from that following CC/hMG treatment. CONCLUSION: The chance of pregnancy is not improved by the short-term use of buserelin with hMG, provided adequate follicular phase management is maintained.

Adult↗
PubMed1994

Variations in pituitary-gonadal suppression during intranasal buserelin and intramuscular depot-triptorelin therapy for central precocious puberty. Belgian Study Group for Pediatric Endocrinology.

This study evaluated pubertal development, growth and pituitary-gonadal suppression in 21 patients with central precocious puberty treated with buserelin intranasally and switched after a mean of 2.1 yr to depot-triptorelin given im for 1 year. Arrest or regression of puberty was observed in 12 patients while progression of puberty during therapy was seen in 9 patients (6 on buserelin, 2 on triptorelin and 1 on both therapies). The increment in serum LH and FSH concentrations after sc injection of short-acting triptorelin was greater on buserelin than on triptorelin therapy, particularly in patients with evidence of progression of puberty. Height velocity during therapy showed a reduction which paralleled the decelerating phase of the normal pubertal growth spurt. The rate of bone maturation during therapy was inversely related to pretreatment bone age. Predicted final height showed marked individual variations which were inversely related to predicted adult height before therapy. These data indicate that differences in the nature and route of administration of Gn-RH agonist therapy for central precocious puberty can be of importance for inhibition of pituitary gonadotropin secretion and development of secondary sex characteristics. Height velocity and bone maturation are age-related and the change in predicted adult height depends on pretreatment level.

Administration, Intranasal↗
PubMed1989

Trial of support treatment with human chorionic gonadotrophin in the luteal phase after treatment with buserelin and human menopausal gonadotrophin in women taking part in an in vitro fertilisation programme.

OBJECTIVE: To evaluate the effect of support with human chorionic gonadotrophin in the luteal phase in women taking part in an in vitro fertilisation programme after buserelin and human menopausal gonadotrophin were used to hyperstimulate their ovaries. DESIGN: Controlled group comparison. SETTING: Outpatient department of a private hospital. PATIENTS: 115 Women with indications for in vitro fertilisation, all of whom had at least one embryo transferred. INTERVENTIONS: After suppression of the pituitary with buserelin the ovaries of all the women were stimulated with human menopausal gonadotrophin on day 4 of the luteal phase. Human chorionic gonadotrophin (10,000 IU) was given to induce ovulation, and oocytes were recovered 34 hours later. Embryos were transferred 46 to 48 hours after insemination. Women who had received the 10,000 IU of human chorionic gonadotrophin on a date that was an uneven number (n = 61) were allocated to receive support doses of 2500 IU human chorionic gonadotrophin three and six days after that date. The remaining 54 women did not receive hormonal support. END POINT: Determination of the rates of pregnancy. MEASUREMENTS and main results--Support with human chorionic gonadotrophin did not significantly alter the progesterone or oestradiol concentrations in the early or mid-luteal phase. The mean (range) progesterone concentrations in the late luteal phase in women who did not become pregnant were, however, significantly higher in those who received support (16(9-110) nmol/l nu 8(4-46) nmol/l), and the luteal phase was significantly longer in this group (14 days nu 12 days). The rate of pregnancy was significantly higher in the women who received support than in those who did not (25/61 nu 8/54). CONCLUSIONS: When buserelin and human menopausal gonadotrophin are used to hyperstimulate ovaries support with human chorionic gonadotrophin in the luteal phase has a beneficial effect on in vitro fertilisation.

Adult↗
PubMed1994

Effect of buserelin on pregnancy rates in dairy cows.

Three field trials were carried out to assess the effect of buserelin on the fertility of dairy cows. In the first, 10 micrograms of buserelin was injected on the day of insemination; there were no significant effects on fertility in comparison with untreated control cows. In the second study the cows were injected 12 days after insemination; the mean pregnancy rates to first insemination were 53.4 and 65.4 per cent for the control and treated cows, respectively (P < 0.01) and the mean pregnancy rates to repeat inseminations were 52.9 and 59.4 per cent for the control and treated cows. The mean calving to conception intervals were 91.4 and 85.3 days (P < 0.01) and the incidences of barren cows were 10.2 and 5.2 per cent. In the third study the cows were injected with buserelin either eight days or 10 days after insemination; there were no significant effects on fertility in comparison with untreated control cows.

Animals↗
PubMed1994

Etiology of serum CA-125 in patients with endometriosis treated with a gonadotrophin-releasing hormone agonist (Buserelin).

Fifty-six patients with pelvic endometriosis were treated with a buserelin dosage of 200 micrograms/day s.c. for 6 months. Scoring of the American Fertility Society (AFS) for endometriosis was performed by laparoscopy in all cases before and at the end of therapy. Serum CA-125 and estradiol levels were determined before the treatment, and monthly during therapy and follow-up (6 months; respectively). A slight positive correlation was found between serum CA-125 concentrations before treatment and AFS scores for adhesions only. Before treatment, serum CA-125 values also correlated slightly with total AFS scores of patients with adhesions. At the end of the 6-month therapy, no correlation was found between CA-125 concentrations and second-look AFS scores for implants and/or adhesions. Serum CA-125 and estradiol values were closely parallel to each other during and after therapy with the gonadotrophin-releasing hormone agonist buserelin. In conclusion, (1) adhesions may play a role in the elevation of serum CA-125 levels in endometriosis, and (2) a significant decrease in serum CA-125 values during the buserelin therapy may result from a rather different mechanism, such as ovarian suppression, other than the therapeutic effect of this agent.

Buserelin↗
PubMed1984

Absence of a direct inhibitory effect of the gonadotropin-releasing hormone (GnRH) agonist D-Ser (TBU)6, des-Gly-NH2(10) GnRH ethylamide (Buserelin) on testicular steroidogenesis in men.

The antigonadal effects of GnRH agonists (GnRH-A) are mediated both through pituitary and testicular inhibitory mechanisms in the rat. To investigate these effects in men, we studied patients having no gonadotropin secretion and compared their testicular response to hCG in the absence or in the presence of GnRH-A. Thirteen patients with acquired pituitary hypogonadotropism had plasma testosterone levels below 1.5 ng/ml and no gonadotropin responses to acute GnRH administration (100 micrograms iv). Testicular responsiveness was evaluated using a single im injection of hCG (5000 IU im). Plasma levels of testosterone, dihydrotestosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), and progesterone were determined before and 4, 12, 24, 48, and 72 h after hCG stimulation. The same protocol was also used in the same patients on day 4 of a 6-day course of treatment with the GnRH-A, D-Ser-(TBU)6, des-Gly NH2 GnRH ethylamide (Buserelin) (3 sc injections of 250 micrograms/day). During the first 4 days of GnRH-A administration, plasma LH, FSH, and testosterone levels were measured daily in order to establish the completeness of the gonadotropin deficiency. Before treatment with hCG, plasma testosterone levels were 0.56 +/- 0.15 and 0.96 +/- 0.22 ng/ml (mean +/- SE) in the absence of GnRH-A and during GnRH-A administration, respectively. The administration of hCG elicited a significant increase in plasma testosterone in both situations; integrated testosterone concentrations were 123.7 +/- 24.9 and 155.5 +/- 27.9 ng/ml . 72 h (P greater than 0.1) in the absence of GnRH-A and during GnRH-A administration, respectively. Likewise the ratios of 17-OHP to progesterone, androstenedione to 17-OHP, and dihydrotestosterone to testosterone after hCG injection were similar in the presence or absence of GnRH-A. Since short term administration of buserelin did not inhibit hCG-induced testosterone secretion in patients with gonadotropin deficiency, we suggest that Buserelin does not grossly modify the function of testicular steroidogenesis enzymes. The antigonadal effects of GnRH-A in man appear to be mediated exclusively through the pituitary.

Buserelin↗